Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms
Year: 2020
Type: article
Study design: Observational Study
Abstract: Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide1,2. Although 58 genomic regions have been associated with CAD to date3–9, most of the heritability is unexplained9, indicating additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and meta-analysed results with 194,427 participants previously genotyped to give a total of 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD-associations (P < 5x10-8, in fixed effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leucocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 [p.Ser219Gly]) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell type-specific gene expression and plasma protein levels shed light on potential novel disease mechanisms.
Authors: Kooperberg, Charles, Young, Kristin, North, Kari E, Lin, Wei-Yu, Zhao, Wei, Danesh, John, Graff, Mariaelisa, Sun, Benjamin B, Butterworth, Adam S, Assimes, Themistocles L, Kamstrup, Pia R, Chung, Ren-Hua, Johnson, Andrew D, Watkins, Hugh, Deloukas, Panos, Hazen, Stanley L, Carty, Cara L, Hung, Yi-Jen, Alam, Dewan S, Nielsen, Sune F, Lee, Wen-Jane, Freitag, Daniel F, Wang, Tzung-Dau, Erdmann, Jeanette, Guo, Xiuqing, Surendran, Praveen, Hindorff, Lucia A, Kathiresan, Sekar, Chen, Yii-Der Ida, Eicher, John D, Ho, Weang-Kee, Schunkert, Heribert, Wilk, Jemma B, Pepine, Carl J, Do, Ron, Franceschini, Nora, Peters, Ulrike, Di Angelantonio, Emanuele, Quertermous, Thomas, Chowdhury, Rajiv, Malarstig, Anders, Barnes, Daniel R, Sheu, Wayne H H, Johnson, Julie A, Juang, Jyh-Ming J, Reiner, Alex P, Absher, Devin, Hsiung, Chao A, Waite, Lindsay L, Frossard, Philippe, Majumder, Abdulla Al Shafi, Samani, Nilesh J, Nordestgaard, Børge G, Rotter, Jerome I, Buyske, Steven, Justice, Anne, Rasmussen, Katrine L, Fauman, Eric B, Paul, Dirk S, Saleheen, Danish, Salfati, Elias L, Young, Robin, Chen, Ying-Hsiang, Taylor, Kent D, Spertus, John A, Boerwinkle, Eric, Rader, Daniel J, Rasheed, Asif, Howson, Joanna M M, Quyyumi, Arshed A, Tybjærg-Hansen, Anne, Lee, I-Te
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4297962537